There are many microfluidic devices that could be produced, for example, using the structure presented described by Unger, et al. (Science, 288, 113 (2000)), in which one or more polymer layers with embedded channels are assembled and bonded to a substrate. Such devices permit the pattern on a surface of the polymer layers to be covered and thereby enclose the channels to produce a closed device.
There are two major roadblocks to mass-production of plastic-based lab on chip (LOC) and other microfluidic devices, such as those used for biological, chemical and gas detection applications. The first one is related to the availability of high-throughput fabrication technologies that can be used to pattern materials with features having micron to nanometer scales with high through-put, very good critical dimension (CD) control, and low cost. Standard microfabrication processes like those imported from microelectronics, have severe limitations in that they do not apply for materials other than standard processing resists.
The second limitation is related to the nature of the materials that can be processed. For the above mentioned applications, the materials need to be easily shaped while presenting good chemical, optical and mechanical properties. Traditionally silicon substrates were used with various etching techniques on such materials as quartz. Over the last 10 years several micro and nano structuration methods have been developed that promise solutions for mass production of patterned materials at affordable costs. Nanoimprint lithography, nano-embossing, hot embossing and lithography are the most widely used, and the materials most widely used are quartz, galls, silicon, silicone or hard thermoplastic materials (e.g. polycarbonates, PMMA, etc.).
Processing conditions required for the embossing of the commonly used hard thermoplastic materials require significant applied pressure. High quality replication has been achieved with PMMA materials at 180° C. and a pressure of 100 bar (Studer, et al. Chen, Appl. Phys. Lett., 2002, 80, 3614-3616) while Cameron et al. (Lab Chip, 2006, 6, 936-941) have reported optimized conditions for PCO materials with an embossing temperature of 40-70° C. above Tg and applied forces of 10-20 bar.
However two major issues are impeding the adaptation of those fabrication methods for the LOC and many other applications. Firstly, low cost, hard thermoplastics materials (polycarbonate, polystyrene . . . ) can be easily shaped and patterned, but the assembly (bonding) of thermoplastic parts to form functional and complex devices or systems with adequate sealing is very difficult and limited by the plastic bonding technologies. Hard thermoplastics need pressure and high temperature processing conditions for bonding constitutive elements. Seals around microfluidic channels are required, and this generally requires very good quality mating surfaces, as the channels are typically defined at interfaces between two parts (usually layers). Additionally non-permanent sealing of hard thermoplastics parts, and resealable bonds are not currently possible.
To avoid these difficulties, elastomer silicone materials have been used instead of hard thermoplastics. There are many advantages to using these materials in terms of less brittleness, and better bonding. Furthermore, they provide for flexibility that may be useful for controlling flow of liquids through the channels. The known methods for patterning (replicating micro- or nano-scale features) silicone elastomers such as PDMS have not been successfully produced in high throughput fabrication processes. So while silicone elastomers have significant advantages in terms of producing bonds for layered structures, silicone elastomer-based microfluidic devices remain costly. Furthermore it is difficult to produce multi-layer PDMS (and expensive to bond multiple layers of PDMS and like silicone elastomer) structures.
Two main options for bonding can be used to bond microstructured layers of PDMS: partial thermal curing process of separate patterned layers, which are subsequently brought in contact together for cure completion; and plasma treatment, in which cured PDMS layers are oxidized in O2 plasma, then finally aligned and permanently bonded. Both approaches need an accurate control of first curing and patterning step in order to preserve a sufficient reactivity for the subsequent bonding step. Thus, successive bonding of several layers becomes difficult, given the time and conditions under which the layers must be assembled. While this is possible in a lab, it is difficult or impossible to produce in a high through-put facility. Thermal bonding is made more expensive by the time it takes and power consumed. Plasma treatment requires expensive controls for material manipulation because once a sample is removed from the plasma chamber (which is a costly treatment) the modified surface properties are un-stable, meaning that the bonding procedure needs to be completed rapidly.
In a paper entitled Thermoplastic Elastomer Gels: An Advanced Substrate for Microfluidic Chemical Analysis Systems to Sudarsan et al. (Anal. Chem. 2005, 77, 5167-5173), a novel class of compounds, namely thermoplastic elastomer gels, are disclosed and tested for properties desired of substrates for microfluidic devices. The TPE gels Sudarsan teaches and uses are highly dilute TPE gels having from 9 to 33 wt. % of TPE (SEBS copolymer resin (CP-9000)) and 67-91 wt. % of mineral oil. The TPE gels were produced using vacuum and heating, which is time consuming and expensive.
Sudarsan et al. teaches a straightforward method for fabrication of microchannel structures using SEBS gels, essentially involving a sequence of steps to create one or more impressions of a negative relief structure in the heated elastomer substrate. For example, according to Sudarsan et al., impressions in a gel (33 wt % TPE, 67 wt. % mineral oil) are made by placing a slab of the gel on top of a master mold that has been preheated to ˜110° C. on a hot plate. Within seconds, Sudarsan et al. reports, the elastomer begins to soften and can be gently pressed down by hand for several seconds to make uniform contact with the structures on the mold. After cooling and release, the solidified gel precisely replicates the shape of the structures on the master.
As will be appreciated by those of skill in the art, the oil content and unique structure of gels make them significantly easier to mold. For example, it is well known in the injection molding field that oil added to TPE improves processability of the material. The gel structure is a scaffold of cross-linked molecules having a lower polymer density and therefore requiring less energy to reorganize, than solid polymers.
According to Sudarsan et al., “the gel material inherently adheres to smooth elastomer, glass, or plastic surfaces, allowing static or low-pressure fluidic networks to be easily constructed. In addition, stronger bonds can be achieved either with elastomer or glass surfaces by briefly heating the material at the bond interface to a temperature just below its softening point using a hot plate or handheld heat gun. Bonds to glass surfaces are removable, while bonds between elastomer layers can be made seamless and essentially permanent.”
Sudarsan et al. teaches heating the gel to an intermediate temperature regime (˜60° C.<T<˜90-120° C.), in which structural rearrangements associated with an order-disorder transition permits limited rearrangement of the structure. The upper limit of the intermediate temperature regime varies with the amount of mineral oil, and the oil composition.
At least ⅔ of the material in the gel is mineral oil, and this oil imparts the properties of the gel required for the facile molding technique to be effective. There are nonetheless some drawbacks to the use of these oils in microfluidic applications, and to the gel structure more generally. Firstly, the requirement for producing the gels increases the costs and labour of producing the material, as gels generally are formed by mixing over a significant period of time, under heat and in a vacuum. Secondly certain mechanical properties of the gels, such as rigidity and integrity of the gel, are generally lower than that of solid polymers, which can limit the range of operating temperatures and pressures of devices made of TPE gels. Thirdly, and most importantly for some applications, the permeability of liquids into and out of the gel may limit the kinds of fluids that the microfluidic device can treat. If there is risk of contamination of the sample by the introduction of mineral oil or any impurity contained within the gel, or inversely from absorption of components of a stored fluid into the gel, for example in a given thermal, chemical or mechanical state, or a change therein, the microfluidic device formed of a gel may not be suitable. Also the swelling of gels when in contact with other fluids may further limit the applications of microfluidic devices fabricated from TPE gels, as swelling applies a mechanical pressure that may cause undesired changes fluid dynamics of the overall device.
The surface quality of patterned TPE gels taught by Sudarsan et al. are of concern for many applications. The presence of oil introduces uncertainty and difficulty controlling the surface properties. For example, it is not known how the surface, especially in the neighbourhood of patterned microchannels, is composed. There does not appear to be a patterning technique that can control these surfaces so that they are characterized by a high level of styrene blocks (or EB groups), at the expense of oil. If the surface has high polymer content, it is not known whether the blocks of the copolymer are homogeneous. These parameters are crucial, especially for microfluidic systems, and most especially for systems that require surface modification or treatment. In other areas of research, Applicant has found that oil reduces the surface quality of TPEs leading to highly inhomogeneous surfaces. It does not appear to Applicant that TPE gels are viable alternatives for producing microfluidic devices for a wide range of applications, especially to a majority of applications where introduction of oil into the microfluidic channels is proscribed.
In three works by I. Stoyanov: a thesis (Karlsruhe University) entitled Development of modular microfluidic devices for bioanalytical sensors, and papers entitled “Microfluidic devices with integrated active valves based on thermoplastic elastomers” (Microelectronic Engineering 83 (2006) 1681-1683), and “Low-cost and chemical resistant microfluidic devices based on thermoplastic elastomers for a novel biosensor system” (Mater. Res. Soc. Symp. Proc. Vol. 872 J 11.4 pp. 169-174): thermoplastic elastomers are considered for microfluidic applications.
Stoyanov proposes TPU as a reasonable compromise between performance, technological complexity and price for some microfluidic applications, and notes: that some of the thermoplastics reported to be used for production of microfluidic components (poly(methylmetacrylate) PMMA, polycarbonate, polystyrene) do not have sufficient chemical resistance; that thermoplastic polyolefins (polyethylene, polypropylene) possess a very high chemical resistance and can be easily formed by hot embossing, but have poor sealing characteristics due to their non-elastic properties; and that other classes of materials with extraordinary chemical resistance like fluoropolymers (polytetrafluoroethylene (PTFE) or excellent sealing properties like silicones (PDMS) are difficult to be reliably connected with macrofluidic components, because of their chemical inertness (PTFE) or lack of sufficient mechanical strength (PDMS).
These works use thermoplastic polyurethane elastomer foils TPU (a specific grade of TPE) having a Shore A surface hardness of 85-93. Clearly TPUs were chosen in part because of their surface hardness being only sufficiently less than those of polyethylene, and polypropylene to overcome their sealing problems, because softer materials such as PDMS are stated to lack required mechanical strength.
Because of the relative inelasticity of TPUs, Stoyanov must work with thin foils (100-600 μm thickness) to obtain a required flexibility. Consequently they can not impart features of certain depths. Because of the thin foil structure, Stoyanov was further unable to bond two microstructured foils due to major deformations. Thin foils bend too much, inducing leakage.
It is further noted that Stoyanov required high pressure and temperature (50-120 bars and 140-160° C.) to thermoform the foils, which induces more shrinkage, higher friction and longer cycle time than lower pressure and temperature methods. The thermoforming requires use of metallic molds, and cannot be performed with low-cost molds.
Further still, TPU are not capable of room temperature, atmospheric pressure or low pressure bonding (either permanent or reversible). To bond together TPU parts (or TPU and others plastic substrates), Stoyanov applied pressure to contacting surfaces and they also needed to use treatment involving solvent exposure, or thermal bonding to achieve satisfactory bonds. These treatments, and the pressure needed for bonding, can be detrimental to the preservation of (bio or chemical) surface treatments and/or to the quality of the features patterned on the surface. Delicate features may deform or collapse under the pressure, changing microfluidic behavior of the devices (flow time, capillary effects, etc.) . . . ) of the device, especially if a multi-layered device is desired.
Accordingly it is noted that viable elastomeric materials used in microfluidics have all had Shore A hardnesses above about 85 (i.e. the top end of Shore A-Shore D hardness). The only known exception to this is Sudarsan et al., who teaches a gel having potential problems with integrity. Gels used according to the teachings of Sudarsan et al. have Shore hardnesses in the mid to lower range of the Shore OO scale.
At Nanotech Montreux 2007, applicant submitted a title for a poster presentation but did not present any poster there. The title was: Thermoplastics Elastomeric (TPE) Blocks Copolymers, a New Material Platform for Microfluidics: Proof of Concept for Complex Siphon Valving on CD, and this title was published.
Accordingly there is a need in the art for new materials for use in microfluidic devices that are as easily patterned and bonded as the TPE gels, but not subject to the drawbacks of the TPE gels. In general there is a need for compositions that can be patterned, and bonded to like compositions as well as a variety of other compositions, while providing seals required for very fine channels such as microfluidic channels, and remaining relatively inert and non-reactive to a wide variety of fluids.